This interesting News & Views article in Nature summarizes some recent work on disordered proteins and how they respond to activators and inhibitors. While I don't understand much of the jargon in the article, the overall message is exciting. I found the following excerpts of interest:
The observation of striking differences in the crystal structures of haemoglobin in the presence and absence of oxygen seemed to validate the idea that allostery [the link is my own] can be rationalized, and possibly even quantitatively accounted for, by examining the structural distortions that connect the different oxygen-binding sites... This structural view of allostery has largely guided the field ever since. However, the realization that more than 30% of the proteome — the complete set of proteins found in a cell — consists of intrinsically disordered proteins (IDPs), and that intrinsic disorder is hyper-abundant in allosteric signalling proteins such as transcription factors, raises the possibility that a well-defined structure is neither necessary nor sufficient for signal transmission.
The take-home message of Ferreon and colleagues' work, and the reason that a switch is possible, is that proteins should not be thought of as multiple copies of identical structures that respond uniformly to a signal. Instead, proteins — especially IDPs — exist as ensembles of sometimes radically different structural states. This structural heterogeneity can produce ensembles that are functionally 'pluripotent', a property that endows IDPs with a unique repertoire of regulatory strategies.
I absolutely love that IDP's are currently rewriting the dogmas of much of molecular biology.
